Rosiglitazone attenuates Acute Kidney Injury from hepatic ischemia-reperfusion in mice by inhibiting arachidonic acid metabolism through the PPAR-γ/NF-κB pathway.

BACKGROUND: Acute Kidney Injury (AKI), a prevalent complication of Liver Transplantation (LT) that occurs during the perioperative period has been established to profoundly impact the prognosis of transplant recipients. This study aimed to investigate the mechanism of the hepatic IRI-induced AKI and to identify potential therapeutic targets for treating this condition and improving the prognosis of LT patients. METHODS: An integrated transcriptomics and proteomics approach was employed to investigate transcriptional and proteomic alterations in hepatic IRI-induced AKI and the hypoxia-reoxygenation (H/R) model using TCMK-1 cells and the hepatic IRI-induced AKI mouse model using male C57BL/6 J mice were employed to elucidate the underlying mechanisms. Hematoxylin-eosin staining, reverse transcription quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and Western blot were used to assess the effect of Rosiglitazone (RGZ) on hepatic IRI-induced AKI in vitro and in vivo. RESULTS: According to the results, 322 genes and 128 proteins were differentially expressed between the sham and AKI groups. Furthermore, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomics (KEGG) pathway analyses revealed significant enrichment in pathways related to amino acid and lipid metabolism. Additionally, the Protein-Protein Interaction (PPI) network analysis of the kidney tissues obtained from a hepatic IRI-induced AKI mouse model highlighted arachidonic acid metabolism as the most prominent pathway. Animal and cellular analyses further revealed that RGZ, a PPAR-γ agonist, could inhibit the expression of the PPAR-γ/NF-κB signaling pathway-associated proteins in in vitro and in vivo. CONCLUSIONS: These findings collectively suggest that RGZ ameliorates hepatic IRI-induced AKI via PPAR-γ/NF-κB signaling pathway modulation, highlighting PPAR-γ as a crucial therapeutic target for AKI prevention post-LT.

Long-term mortality and patency after drug-coated balloon angioplasty in the hemodialysis circuit: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: To compare all-cause mortality and primary patency with drug-coated balloon angioplasty (DCBA) compared with plain balloon angioplasty (PBA) in people with hemodialysis-related stenosis. MATERIALS AND METHODS: PubMed, Embase, and Cochrane Library databases were searched from November 1966 to February 2021 to identify randomized controlled trials (RCTs) that assessed the use of DCBA versus PBA for stenosis in hemodialysis circuits. Data extracted from the articles were integrated to determine all-cause mortality, target lesion primary patency (TLPP), circuit access primary patency (CAPP), 30-day adverse events, and technical success for the two approaches. We performed meta-analysis on these results using a fixed-effects model to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) where I2 < 50% in a test for heterogeneity, or a random-effect model if otherwise. Sensitivity and subgroup analyses were also performed. RESULTS: Sixteen RCTs of 1672 individuals were included in our meta-analysis, of which 839 individuals received DCBA and 833 received PBA. The pooled outcome showed no statistical difference between DCBA and PBA in all-cause mortality at 6 months (OR = 1.29, 95% CI = 0.72-2.32, p = 0.39, I2 = 4%), 12 months (OR = 1.02, 95% CI = 0.68-1.53, p = 0.91, I2 = 0%), and 24 months (OR = 1.50, 95% CI = 0.87-2.57, p = 0.15, I2 = 0%), 30-day adverse events (OR = 1.09, 95% CI = 0.30-3.98, p = 0.90, I2 = 66%), and technical success (OR = 0.18, 95% CI = 0.02-1.92, p = 0.16, I2 = 65%). The DCBA had significantly better outcomes versus PBA in TLPP at 6 months (OR = 2.37, 95% CI = 1.84-3.04, p < 0.001, I2 = 44%) and 12 months (OR = 1.77, 95% CI = 1.22-2.56, p = 0.002, I2 = 56%), and CAPP at 6 months (OR = 2.07, 95% CI = 1.21-3.54, p = 0.008, I2 = 67%) and 12 months (OR = 1.66, 95% CI = 1.29-2.15, p < 0.001, I2 = 0%). CONCLUSION: In hemodialysis circuit stenosis, DCBA appears to have similar safety but greater efficacy than PBA.

Acellular Vascular Scaffolds Preloaded With Heparin and Hepatocyte Growth Factor for Small-Diameter Vascular Grafts Might Inhibit Intimal Hyperplasia.

To develop small-diameter (<6 mm) scaffolds capable of accelerating rapid endothelialization and improving long-term patency rate, we created acellular vascular scaffolds preloaded with heparin and hepatocyte growth factor (HGF). Heparin was conjugated to suppress thrombogenic responses, and HGF was immobilized to induce endothelial cells (ECs) proliferation and migration. The scaffolds immobilized with heparin exhibited highly effective localization and sustained release of HGF for 30 days in vitro. We implanted this modified scaffold into the carotid artery of a rabbit model to investigate the efficacy in vivo. The acellular vascular scaffold with heparin only was used as control. After transplantation, the patency of this modified scaffold was 91.67% at 1, 3, 6, and 12 months, while the patency rate in the group with grafted heparin only was 83.33% at 1, 3, 6, and 12 months. This modified scaffold significantly stimulated ECs proliferation and the endothelium aligned in the direction of flow after 12 months. In addition, intimal hyperplasia was significantly reduced in the grafts coated with HGF compared with the control grafts. The small-diameter vascular grafts with an inner diameter of 2.5 mm preloaded with heparin and HGF may be a substitute for autologous blood vessels in clinic.

Comparative effectiveness and safety among different tip-design hemodialysis long-term catheters: A meta-analysis.

PURPOSE: The aim of this meta-analysis is to compare effectiveness and safety among different tip-design long-term hemodialysis (HD) catheters. MATERIALS AND METHODS: PubMed, Embase, and Cochrane Library databases were searched until 8 December 2021 to identify randomized controlled trials (RCTs) and cohort studies comparing step-tip, split-tip, or symmetrical-tip design catheters in patients undergoing HD will be included. The Cochrane Risk of Bias tool and the Newcastle-Ottawa Scale were used to evaluate the quality of RCTs and cohort studies. Data extracted from the articles were integrated to determine mean effective blood pump velocity (Qb), blood recirculation rates, secondary patency, catheter-related infection, catheter-related blood stream infection (CRBSI), thrombosis rates, and all-cause mortality for the three tip-designs. We performed meta-analysis on dichotomous outcomes using a random-effects model to evaluate risk ratios (RRs) and 95% confidence intervals (Cls). The effect sizes of continuous outcomes were reported as the mean difference (MD). Sensitivity and subgroup analyses were also performed. The study was registered in the PROSPERO (CRD42021297069). RESULTS: Six RCTs and 11 cohort studies of 2617 individuals were included in our meta-analysis, of which 1088 individuals inserted split-tip catheters, 897 individuals inserted step-tip catheters and 650 received symmetrical-tip design catheters. Sym-tip performed better in mean Qb (MD = 43.85, 95% Cl = 18.13-69.56, p = 0.0008) than step-tip. Split-tip had better outcomes vs step-tip in blood recirculation (RR = 3.44, 95% Cl = 2.49-4.39, p < 0.00001). Sym-tip had significantly better outcomes compared with step-tip (RR = 0.28, 95%Cl = 0.09-0.81, Z = 2.34, p = 0.02) and split-tip (RR = 0.19, 95% Cl = 0.09-0.43, p < 0.0001) in thrombotic events. No significant difference was found in secondary patency, infection rates, CRBSI, and all-cause mortality among the three tip-designs. CONCLUSION: The sym-tip of tunneled cuffed catheters performed better mean Qb, lower thrombotic events, and lower blood recirculation when blood line reversed, which may have an advantage over other two catheter-tips.

Long-term patency and comparisons of venous outflow in hemodialysis forearm arteriovenous grafts.

INTRODUCTION: This retrospective study investigated the factors and the effects of different venous outflows on forearm arteriovenous graft patency. METHODS: The venous outflow sites included basilic, cephalic, median antecubital, and deep veins. Comparisons among multiple groups were analyzed. FINDINGS: A total of 179 patients with forearm loop arteriovenous grafts met the inclusion criteria. Of these, 72 were basilic, 48 were cephalic, 44 were median antecubital, and 15 were deep. The median observation period was 19 months. The survival rate was 84.9% at 24 months and 78.2% at 48 months. Primary, secondary, and assisted primary patency rates for all arteriovenous grafts were 48.9%, 72.4%, and 68.4% at 12 months; 13.8%, 33.9%, and 23.6% at 24 months; and 0.6%, 4.6%, and 2.3% at 48 months, respectively. Differences in primary patency were statistically significant compared with those of secondary and assisted primary patency (P < 0.05). Primary patency rates for cephalic, median antecubital, basilic, and deep were 47.9%, 48.6%, 47.7%, and 40.0% at 12 months and 12.5%, 13.9%, 22.7%, and 0% at 24 months, respectively. Secondary patency rates for cephalic, median antecubital, basilic, and deep were 75.0%, 69.4%, 75.0%, and 73.3% at 12 months and 39.6%, 30.6%, 38.6%, and 13.3% at 24 months, respectively. There was no significant difference in primary thrombosis among basilic, cephalic, median antecubital and deep. There were no significant differences observed in primary or secondary patency rates among all the groups. Stenoses in the venous anastomosis and outflow vein were frequently observed in all types of arteriovenous grafts. Central venous stenosis was most commonly seen in deep (26.67%). On average, 1.9 interventions per patient were performed on the graft to maintain function. CONCLUSION: Different venous outflow selections were not associated with long-term patency and the occurrence of thrombosis in hemodialysis forearm loop arteriovenous grafts.

Surgical repair of a special category of arteriovenous fistula outflow stenosis caused by venous valve hyperplasia.

OBJECTIVE: This study evaluated a special category of arteriovenous fistula outflow stenosis caused by venous valve hyperplasia and explored the effectiveness of surgical repair in dealing with this kind of stenosis. STUDY DESIGN: This retrospective cohort study was conducted from February 2016 to January 2020 in our center. Patients with arteriovenous fistula dysfunction, including flow rate insufficiency, venous hypertension, thrombosis, and aneurysm dilation enlargement, were selected. Stenosis lesions presenting with venous valve hyperplasia were selected after ultrasound screening. All patients underwent surgical repair and were followed up every 6 months after surgery. RESULTS: Forty-three patients (median age, 54.5 ± 11.2 years; 65.1% men) were included. All procedures were technically successful. Based on intraoperative exploration, 56.5% were reconstructed via autologous vein patch, 17.4% of patients were reconstructed with end-to-end reconstruction after cutting the stenotic segment, 13.0% of cases simply had the valve resected, and 13.0% of cases involved a longitudinal incision and transverse suture. All patients returned to routine dialysis the following day and avoided catheter insertion. The mean follow-up time was 22.5 ± 14.0 (range, 1.3-49.8) months. The patency rates at 2 and 4 years were 92.2% and 79.0%, respectively. Valves harvested from patients were analyzed via Masson staining and immunohistochemical staining, indicating collagen fiber and myofibroblast hyperplasia in outflow venous valve hyperplasia (OVVH). CONCLUSIONS: Outflow venous valve hyperplasia can lead to fistula dysfunction. Ultrasound is the main method to diagnosis OVVH. Special surgical repair can preserve valuable vascular resources and relieve stenosis, is safe and effective, and has a high patency rate.

[12]aneN3-based lipid with naphthalimide moiety for enhanced gene transfection efficiency.

Three cationic lipids derived from [12]aneN3 modified with naphthalimide (1a), oleic acid (1b) and octadecylamine (1c) were designed and synthesized. In vitro transfection showed that all these liposomes can deliver plasmid DNA into the tested cell lines. Among these liposomes, 1a gave the best transfection efficiency (TE) in A549 cells, which was higher than that of lipofectamine 2000. More importantly, the TE of 1a was dramatically increased in the presence of 10% serum. These results suggested that 1a might be a promising non-viral gene vector, and also give further insight for developing novel high performance gene delivery agents.

Dihydropyridine-derived BODIPY probe for detecting exogenous and endogenous nitric oxide in mitochondria.

A mitochondria-targetable probe Mito-DHP for nitric oxide (NO) was designed and synthesized by introducing dihydropyridine and triphenylphosphonium (TPP) moieties into boron dipyrromethene (BODIPY) dye. Mito-DHP was able to effectively detect nitric oxide through the aromatization of dihydropyridine to fluorescent pyridine product under oxygen-free conditions. The probe Mito-DHP showed high selectivity to NO over a number of reactive oxygen/nitrogen species (ROS/RNS) as well as high sensitivity (detection limit at 25nM), pH stability and bio-compatibility. Furthermore, Mito-DHP proved to target mitochondria specifically and to visualize both exogenous and endogenous NO in real time.

Aromatization of 9,10-Dihydroacridine Derivatives: Discovering a Highly Selective and Rapid-Responding Fluorescent Probe for Peroxynitrite.

As part of an effort to develop generally applicable strategies for creating probes suitable for detecting important molecular and ionic species, the oxidative aromatization of nonfluorescent 9,10-dihydroacridine derivatives triggered by peroxynitrite (ONOO-) led to the identification of compound 2H, 9-phenyl-9,10-dihydroacridine-4-carboxylic acid, as a rapid-responding fluorescent probe capable of detecting ONOO- with an extraordinary selectivity. Adding a little more than 1 equiv of ONOO- to a solution of 2H resulted in over 100-fold fluorescence enhancement. In sharp contrast, treating 2H with excessive amounts of other oxidants that often interfere with the detection of ONOO- failed to lead to noticeable fluorescence increase. The reaction of ONOO- with 2H shows a similar efficiency in the pH range of 2-8. Low cytotoxicity was observed for 2H and its aromatized product. Bioimaging experiments revealed the promising potential of 2H as a new fluorescent probe for the selective detection of intracellular ONOO-.

NO-Responsive vesicles as a drug delivery system.

A rationally designed amphiphile containing a hydrophobic Hantzsch ester and a hydrophilic phosphate ester was able to form vesicles in aqueous solution, and resulted in the first example of a NO-responsive drug delivery system.

Gemini-Type Tetraphenylethylene Amphiphiles Containing [12]aneN3 and Long Hydrocarbon Chains as Nonviral Gene Vectors and Gene Delivery Monitors.

Four gemini amphiphiles decorated with triazole-[12]aneN3 as the hydrophilic moiety and various long hydrocarbons as hydrophobic moieties, 1-4, were designed to form micelles possessing the aggregation-induced emission (AIE) property for gene delivery and tracing. All four amphiphiles give ultralow critical micelle concentrations, are pH-/photostable and biocompatible, and completely retard the migration of plasmid DNAs at low concentrations. The DNA-binding abilities of the micelles were fully assessed. The coaggregated nanoparticles of 1-4 with DNAs could convert back into AIE micelles. In vitro transfections indicated that lipids 1 and 2 and their originated liposomes bearing decent delivering abilities have great potentials as nonviral vectors. Finally, on the basis of the transfection and the transitions between condensates and micelles, lipid 2 was singled out as the first example for real-time tracing of the intracellular deliveries of nonlabeled DNA, which provides spatiotemporal messages about the processes of condensate uptake and DNA release.

[Surgical management of penetrating cervical vascular trauma].

OBJECTIVES: To discuss diagnosis and surgical management of penetrating cervical vascular trauma. METHODS: A retrospective clinical analysis of 22 penetrating carotid artery injuries. RESULTS: Twenty-two patients presented 32 vascular injuries, including innominate artery (n = 1), innominate vein (n = 2), subclavian artery (n = 6), subclavian vein (n = 2), common carotid artery (n = 3), internal carotid artery (n = 3), external carotid artery (n = 4), jugular vein (n = 8) and vertebral artery (n = 4). There were 12 patients with stab wounds, 2 with blast wound and 8 with iatrogenic injuries. Of these, there were 12 zone-1 injuries (38%), 19 zone-2 injuries (59%) and 1 zone-3 injury (3%). The distribution of 4 vertebral artery injuries were V1 (n = 1), V2 (n = 2) and V3 (n = 1). All patient received surgical and endovascular managements and got survival. CONCLUSIONS: Patients with penetrating cervical vascular injuries have high rate of mortality. Emergent surgical exploration is necessary for patients with hard signs of vascular injury such as hemodynamic instability, exsanguinating hemorrhage, or expanding hematoma. Those patients that are hemodynamically stable and who are without respiratory compromise should undergo further diagnostic imaging evaluation.